title: HSP90 beta regulates rapsyn turnover and subsequent AChR cluster formation and maintenance.
abstract: Rapsyn, an acetylcholine receptor (AChR)-interacting protein, is essential for synapse formation at the neuromuscular junction (NMJ). Like many synaptic proteins, rapsyn turns over rapidly at synapses. However, little is known about molecular mechanisms that govern rapsyn stability. Using a differential mass-spectrometry approach, we identified heat-shock protein 90beta (HSP90beta) as a component in surface AChR clusters. The HSP90beta-AChR interaction required rapsyn and was stimulated by agrin. Inhibition of HSP90beta activity or expression, or disruption of its interaction with rapsyn attenuated agrin-induced formation of AChR clusters in vitro and impaired the development and maintenance of the NMJ in vivo. Finally, we showed that HSP90beta was necessary for rapsyn stabilization and regulated its proteasome-dependent degradation. Together, these results indicate a role of HSP90beta in NMJ development by regulating rapsyn turnover and subsequent AChR cluster formation and maintenance.
authors.affiliation: Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Luo
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Xian-Ping
authors.initials: XP
authors.lastname: Dong
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Tao
authors.forename: Annie
authors.initials: A
authors.lastname: Ting
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhou
authors.forename: James
authors.initials: J
authors.lastname: Meixiong
authors.forename: Junjie
authors.initials: J
authors.lastname: Luo
authors.forename: F C Alex
authors.initials: FC
authors.lastname: Chiu
authors.forename: Wen C
authors.initials: WC
authors.lastname: Xiong
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology; D009124:Muscle Proteins / Q000378:metabolism* / Q000502:physiology; D032446:Myoblasts / Q000502:physiology; D011247:Pregnancy; D011940:Receptor Aggregation / Q000235:genetics; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*
chemical_list: D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; D035683:MicroRNAs; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; C051609:peripheral membrane protein 43K